M. A. O'Leary

Experimental images of heterogeneous turbid media by frequency-domain diffusing-photon tomography

We present images of heterogeneous turbid media derived from measurements of diffuse photon-density waves traveling through highly scattering tissue phantoms. To our knowledge, the images are the first experimental reconstruction based on data collected in the frequency domain. We demonstrate images of both absorbing and scattering heterogeneities and show that this method is sensitive to the optical properties of the heterogeneity. The algorithm employs a differential measurement scheme that reduces the effect of errors resulting from incorrect estimation of the background optical properties. The relative advantages of sources with low and high modulation frequency are discussed within this context.

Fluorescence lifetime imaging in turbid media

The lifetime of a f luorophore generally varies in different environments, making the molecule a sensitive indicator of tissue oxygenation, pH, and glucose. However, lifetime measurements are complicated when the f luorophore is embedded in an optically thick, highly scattering medium such as human tissue. We formulate the inverse problem for f luorescence lifetime tomography using diffuse photon density waves, and we demonstrate the technique by deriving spatial images of heterogeneous f luorophore distribution and lifetime, using simulated measurements in heterogeneous turbid media.

Detection and characterization of optical inhomogeneities with diffuse photon density waves: a signal-to-noise analysis

Diffusing photons provide information about the optical properties of turbid media. In biological tissues these optical properties may be correlated to physiological parameters, enabling one to probe effectively the physiological states of tissue for abnormalities such as tumors and hemorrhages. We show that positional uncertainty in the source and detector lead to significant random errors that degrade the optical information available from diffusing photons. We investigate the limits for the detection, localization, and characterization of optical inhomogeneities by using diffusing photons as a probe. Although detection is sufficient for tumor screening, full characterization of the optical properties is desirable for specification of the tumor. Our findings in model breast systems with realistic signal-to-noise ratios indicate that tumors as small as 0.3 cm in diameter can be unambiguously detected; however, simultaneous determination of tumor size and optical properties is possible only if its diameter is of the order of 1.0 cm or larger. On the other hand, if a priori information about the size (optical properties) is available, then the optical properties (size) of tumors as small as 0.3 cm in diameter can be determined.

Fluorescent diffuse photon density waves in homogeneous and heterogeneous turbid media: analytic solutions and applications

We present analytic solutions for fluorescent diffuse photon density waves originating from fluorophores distributed in thick turbid media. Solutions are derived for a homogeneous turbid medium containing a uniform distribution of fluorophores and for a system that is homogeneous except for the presence of a single spherical inhomogeneity Generally the inhomogeneity has fluorophore concentration, and lifetime and optical properties that differ from those of the background. The analytic solutions are verified by numerical calculations and are used to determine the fluorophore lifetime and concentration changes required for the accurate detection of inhomogeneities in biologically relevant systems. The relative sensitivities of absorption and fluorescence methods are compared.

Reradiation and imaging of diffuse photon density waves using fluorescent inhomogeneities

Abstract Experiments demonstrate the reradiation of diffuse photon density waves in turbid media by an obstacle filled with fluorescent dye. The reradiated energy was also in the form of a diffuse density wave that was readily detected at the red-shifted energy. In this process the inhomogeneity was converted into a source of diffuse photon density waves, and localization of the object can be accomplished by analysis of the reradiated wavefronts. We will discuss these measurements and demonstrate some simple practical devices which are capable of localizing the center of such a fluorescent inhomogeneity.

Simultaneous scattering and absorption images of heterogeneous media using diffusive waves within the Rytov approximation

In this work we compare the Born and Rytov approximations for frequency-domain diffusing wave tomography. We confirm that the Rytov approximation gives a more accurate reconstruction of the absorptive properties. In addition, the natural separation of amplitude and phase within the Rytov approximation presents the possibility for image reconstruction algorithms which use either the phase shift or the amplitude decay of the diffusive waves. We demonstrate this effect, and apply these algorithms to simultaneously reconstruct the scattering and absorption properties of heterogeneous turbid media.

Photon migration within the P3 approximation

The diffusion approximation to the photon transport equation is the simplest model for photon migration. The applicability of the diffusion approximation, however, is limited. For example, it is strictly valid only when the absorption coefficient is small compared to the scattering coefficient and the source modulation frequency is small compared to the scattering rate. In this contribution we establish the theoretical range of validity of the diffusion approximation, review a frequency-dependent solution of the transport equation within the P3 approximation, and establish the significance of the P3 solution using Monte Carlo computer simulations. We find that the P3 approximation, in most cases, permits a more accurate determination of the optical properties of highly absorbing media as well as from data obtained at modulation frequencies greater than 3 GHz. Interestingly, for highly anisotropic scattering (g equals 0.9), we find that diffusion theory and the P3 approximation predict approximately the same values for the reduced scattering coefficient.

Breast tumor detection using continuous wave light source

The detection of small amounts of indocyanine green (ICG) in small volumes would suggest its potential use in the detection of early breast tumors. While phased array has already shown its ability to sharply localize small amounts of ICG in the picomole region, the question has arisen, what would be the comparable sensitivity of continous light systems for the same purpose? If this were a comparable sensitivity, the advantages of the simplest of opto- electronic systems and the use of light intensity not limited to those available under FDA regulations for laser diodes could be realized. In this research work, we investigate two methods of enhancing the contrast agent between diseased and healthy tissue using low frequency amplitude modulated light sources. The first method exploits the symmetry between the left and right breast and the second exploits the cylindrical symmetry of the breast. Both effect are enhanced by the use of an injected contrast agent (ICG). Based on the theory and model study, several human subjects cases were studied in the Hospital of the University of Pennsylvania. The results show that the peak signal can get about 60 seconds after ICG injection through the vein and then will take few minutes to get back to the baseline. The half decay time and maximum (Delta) OD are dependent of the characteristics of the breast tissue.

Optics for diffuse photon density waves

We perform experiments which confirm the existence of diffuse photon density waves in homogeneous diffusive media and show that these waves obey some simple principles of optics. In particular, experiments are done to show that Snells law holds for waves moving across a boundary between media of different diffusional indices of refraction. Other experiments are performed which investigate the scattering of these waves from spherical objects, and simple models are presented to explain these results. Finally we demonstrate that it is possible to excite a fluorescent object with a diffuse photon density wave, creating a transduced diffuse photon density wave with a different wavelength. In summary we discuss the implications of these results for medical imaging.